Intox, detox, antidotes – Evidence based diagnosis and treatment of acute intoxications

Abstract

Background and aim

Aim of this review is to describe the role of clinical toxicology in the context of acute medicine. A special focus is put on antidotes and important aspects of diagnosis and therapy of acute intoxications. The data of the annual report of GIZ-Nord Poisons Centre is analyzed concerning the following aspects: what intoxications are relevant in acute medicine, are there special aspects in therapy, e.g. antidotes, and what antidotes are relevant? More over intoxication-related fatalities are analyzed.

Results and conclusion

In 2015 the poisons centre was consulted in 33,000 cases of acute intoxications. The most important groups are drugs (e.g. antidepressants, beta blockers and calcium channel blockers), chemical products (e.g. products containing surfactant, corrosive substances and toxic alcohols like methanol), plants and recreational drugs. Intoxications are relevant in acute medicine. Some substances can cause fatal intoxications. Important antidotes are naloxone for opiods, acetylcystein for paracetamol, fomepizole and ethanol for toxic alcohols and diazepam for intoxications caused by chloroquine.

Introduction

History can be seen as a history of poisons and antidotes: There are innumerable examples in mythology and history (Fig. 1). Socrates was sentenced to death by drinking a concoction of hemlock because he was found guilty of impiety and of corrupting the minds of the youth. Mithridatis VI, king of Pontus and Armenia minor (130–63 BCE) on the other hand devoted his life to finding a universal antidote; a so-called “mithridate” [1].

In the context of acute medicine, intoxications do not represent the largest group of diseases, like e.g. stroke, infections or heart attacks, but in Germany they are responsible for about 5% of all cases in emergency medicine [2]. In France the situation is comparable [3], but there do not exist exact data for the whole of Europe.

This is the background of a review of data from GIZ-Nord Poisons Centre.

GIZ-Nord is the poisons centre for the four federal states in Northern Germany (Bremen, Hamburg, Lower Saxony and Schleswig-Holstein) with a population of 13 million people. Approximately twelve doctors plus three nurses give consultations on the phone in a 24/7 service.

It is contacted approximately 37,000 times per year, both by the public and professional medical personnel, especially doctors who work in acute medicine.

The data are extracted from the annual report for 2015 and comprise approximately 33,000 intoxications [4].

Detailed analyses are conducted in the following fields:

• demographic data, like age and sex

• grading of the intoxication according to the PSS (Poisoning Severity Score, explanation see below)

• analysis of the toxindex (explanation see below)

• groups of toxic substances (18 groups, e.g. medical drugs, plants, animals, chemical products, recreational drugs)

• circumstances of the intoxication, e.g. suicidal, accidental, occupational

The Poisoning Severity Score (PSS) describes the severity of an intoxication. There are five grades: fatal, severe, moderate, minor and no symptoms. Findings from 14 organs or organ systems (e.g. nervous system, liver, kidney, metabolism) are taken into account for the grading. World wide the PSS is used by the largest number of poisons centres [5].

The toxindex is an appropriate index for the toxicity of substances or substance groups. It is calculated as the percentage of all fatal, severe and moderate intoxications in relation to the total number of all intoxications of the substance.

The objective of this review was to provide relevant and concise information concerning intoxications in the context of acute medicine. For this purpose the following questions were formulated and aim of the study were these topics:

What intoxications have a special relevance for acute medicine?

Are there specific diagnostic or therapeutic features, that should be known by doctors working in acute medicine?

What antidotes are relevant in acute medicine?

The number of intoxications in the main groups of noxious substances can be depicted from Fig. 2. The largest groups are intoxications with medical drugs (n = 12,532) and chemical products (n = 8743).

The total number of intoxications with medical drugs was 12,532. There were nine fatalities, 733 severe and 2229 moderate intoxications. Hence the overall toxindex was 23.7%.

The drugs were chosen from the perspective of a poisons centre, i.e. these intoxications feature special aspects in clinical toxicology.

The largest subgroup with more than half of all cases of medical drug intoxications were substances with an effect on the nervous system. Altogether these were 6297 cases. This group comprises analgetic drugs, like paracetamol or opiods, and antidepressant or antipsychotic drugs, like amitriptyline, quetiapine or opipramole. Moreover antiepileptic drugs belong into this group.

The overall toxindex of this group was 35% including nine intoxication-related fatalities (see Table 1).

The analgetic drugs paracetamol and opioids are of special interest, since there do exist specific antidotes: acetylcysteine to reduce the liver damage caused by paracetamol and naloxone to treat the respiratory depression caused by opioids.

From the other groups some substances were chosen, because they feature special aspects of clinical toxicology. They comprise drugs with an effect on the cardiovascular system, the hormonal system and antimalaria medication.

Beta blocking agents: 266 cases with 84 severe or moderate intoxications, toxindex 31.6%.

Calcium channel blockers: 116 cases with 38 severe or moderate intoxications, toxindex 33%.

Contraceptive pills: 212 cases with one moderate intoxication, toxindex 0.5%.

Thyroid hormones: 284 cases with one severe and three moderate intoxications, toxindex 1.4%.

Chloroquine (antimalaria drug): six cases, including one severe case with the application of the antidote diazepam.

In our review we found fairly high figures for the toxindex of beta blockers, calcium channel blockers and tricyclic antidepressants. The three groups are by all means critical, if a patient intoxicates himself deliberately with these medical drugs. The symptoms of these intoxications are cardiovascular (e.g. dysrythmias, hypotension, bradycardia, tachycardia), central nervous symptoms, like convulsions, or symptoms of renal, liver or metabolic impairment.

The treatment is usually symptomatic, but there do exist some specific antidotes for some medical drugs. Most doctors know the antidote acetylcysteine for paracetamol intoxication and naloxone for the treatment of respiratory insufficiency caused by an opioid intoxication. Table 3 summarizes the most important and relevant antidotes for acute intoxications.

A rather not very well known one is the antidote for chloroquine intoxications. Chloroquine is an antimalaria drug and often used in Africa. There the antidote was detected: It is the well known drug diazepam and the story of its dicovery is rather interesting. Patients with a monointoxication with chloroquine often died due to dysrythmias and other cardiovascular symptoms. When the patient had tried to commit suicide with chloroquine plus diazepam they survived. The mechanism is not understood yet, though we know about benzodiazepine receptors in the heart. But the role of these receptors is still to be elucidated.

This second largest group comprises a broad variety of different products: from rather harmless dishwashing agents or shampoo (containing surfactant) to corrosive drain cleaners and the toxic alcohols methanol and ethylene glycole.

In the surfactant group normally no severe symptoms occur with one exception: very old and dement patients, especially in nursing homes for the elderly, drink large amounts of these liquids. These patients have a risk to aspirate the surfactant, develop severe pneumonia and can die [7].

Certainly corrosive substances, like drain cleaners or some other products can cause corrosions in the gastrointestinal tract when they are swallowed. With the exception of hydrofluoric acid (antidote: calcium gluconate) there is no antidote and therapy is symptomatic. The 68 intoxications with drain cleaners (21 severe and moderate cases) had a toxindex of 31%.

Another group are the toxic alcohols methanol and ethylene glycol, since they have some interesting diagnostic and therapeutic implications. Methanol can develop, when alcoholic spirits are produced illegally. There are several epidemics with sometimes hundreds of intoxication-related fatalities with methanol; e.g. in Russia, Estonia, Norway and the Czech Republic only recently [8], [9], [10]. Moreover methanol is found in fuel for model airplanes.

Ethylene glycol is the other toxicologically relevant toxic alcohol. It is found in anti freezing products, e.g. for cars.

Both toxic alcohols are metabolized similarly by the same enzyme, alcohol dehydrogenase and the metabolites are responsible for the toxic effects. Metabolites of methanol cause acidosis and ocular symptoms whereas the metabolites of ethylene glycol cause acidosis plus renal impairment. The toxicity of both toxic alcohols can be minimized by antidotes. The enzyme alcohol dehydrogenase can be blocked by normal ethanol or by the specific antidote fomepizole. Since fomepizole is rather expensive and not always available, ethanol can be used as an effective antidote for the relevant intoxication with toxic alcohols.

There were 81 intoxications with antifreezing products that usually contain ethylene glycole. The eleven severe and moderate intoxications result in a toxindex of 14%. One of the severely intoxicated patient with a pronounced acidosis was treated with the antidote ethanol and hemodialysis was performed.

Especially during the weekend nights the poisons centres are consulted very often concerning intoxications with these drugs. Apart from well known drugs, like cocaine, heroine (antidote naloxon), marihuana or classic ecstasy, there has been a dramatic increase with so called novel psychoactive substances during the last years [11]. This new group comprises cathinone-like drugs, amphetamine-like drugs, synthetic cannabinoids and synthetic opiods.

The synthetic cannabinoids are a difficult group due to several aspects. They are dangerous, if you look at the toxindex of 49% compared to other noxious substances.

Whereas regular cannabis is usually no big toxicological problems (hardly ever severe or fatal intoxications), the patients with an overdose of synthetic cannabinoids often develop dramatic intoxications. Extreme hypokalemia and cerebral convulsions can occur. Often these products have banalizing names like “Jamaican Spirit” or “Monkeys go Banana”. Patients should be treated in ICU and toxicological analysis should be performed. There is no specific antidote.

Altogether 796 intoxications with recreational drugs were registered. This group includes well known “classic” drugs like cocaine, heroine, ecstasy, LSD and some more. On the other hand NPS (novel psychoactive substances) are included. Intoxications with these substances increased dramatically during the last years.

The overall toxindex for the intoxications with recreational drugs was 49%.

When toddlers eat small parts of garden plants or plants in the house, this is usually- with some rare exceptions- no big problem [12].

When plants are ingested deliberately in suicidal purpose this can be a major problem when the plant yew (Taxus baccata) is used. Patients prepare a concoction especially from the leaves and drink this. GIZ-Nord had one fatal case in the year 2015. The toxins cause cardiovascular and central nervous symptoms. There is no specific antidote.

In 2015 there were 2975 intoxications caused by plants. The vast majority, 2398 cases representing more than 80%, were due to an accidental exposition in children. In most cases only minor symptoms developed. On the other hand there were some severe intoxications with rhododendron, giant hogweed and one fatal case after the suicidal ingestion of a concoction made from the plant yew (Taxus baccata, Fig. 3).

A small, nevertheless relevant, topic are envenomations with exotic pets, e.g. rattle snakes and black mambas. In these cases the poisons centres can be a great help for finding the appropriate antivenom. They have lists and contact details of the institutions which store the antivenoms, especially for indigenous and exotic snakes; sometimes zoos, but usually university hospitals.

The total number of cases was 314 for the year 2015. The toxindex was 19% and five severe intoxications developed, four of them caused by snake bites.

In 2015 GIZ-Nord detected 16 intoxication related fatalities. Among these fatalities six patients were female, eight men and in two cases the sex was unknown. The youngest patient was a 16-year old girl and the oldest one was a male patient of 93 years. In nine cases the toxic substance was a medical drug and one male patient of 40 years of age successfully committed suicide by drinking a concoction made of the plant yew (Taxus baccata). All intoxication related fatalities are summarized in table 1.

This number appears low, but mainly patients that reach hospitals alive are recorded by a poisons centre. In nine cases the toxic substance was a medical drug; most of them were antipsychotic or antidepressant drugs, e.g. amitriptyline, a classic tricyclic antidepressant. Whereas the majority of the cases was suicidal, there was at least one tragic case of an 18-years old young man, who drank hydrofluoric acid accidentally. The liquid had been put into another bottle and the young man drank the liquid thinking it was mineral water. Important to know that there is a special antidote for hydrofluoric acid: calcium gluconate.